52 results about "Liraglutide" patented technology

The present invention relates to a process for preparing Liraglutide by solid phase peptide synthesis (SPPS). It describes a convergent synthesis by using different fragments including pseudoprolines in one or more of the fragments bound to a solid support.

The invention relates to the field of biological medicine preparation, and particularly provides liraglutide precursor peptide tandem recombinant fusion protein, polynucleotide, recombinant expression plasmid, engineered host cell and a method for preparing target polypeptide. The recombinant fusion protein is fusion peptide-target polypeptide-(linker peptide-target polypeptide) n from the N terminal to the C terminal, n is a positive integer from 4 to 6, the fusion peptide is SEQ ID NO.1, the target polypeptide is liraglutide precursor peptide, the linker peptide comprises a spacer peptide and a protease restriction enzyme cutting site, the spacer peptide is SEQ ID NO.2, the isoelectric point of the recombinant fusion protein is 4.6-4.7, and the average hydrophilic value is-0.780--0.765. The proportion of the target polypeptide in the recombinant fusion protein is high, use of solvents under extreme conditions is avoided in the production process, the enzyme digestion efficiency is high, and the product purity and yield are high.

The invention belongs to the technical field of biological medicine, and relates to an oral peptide drug delivery system based on a soybean trypsin inhibitor and core-shell hydrogel, the oral peptide drug delivery system comprises therapeutic polypeptide, KTI and a core-shell structure gel matrix, and the problems that an existing oral peptide delivery system is passively protected and drug burst release is remarkable are solved. A chitosan / sodium tripolyphosphate ionic cross-linked network forms an inner core, a sodium alginate / calcium ion'egg box 'structure cross-linked network forms a shell, and therapeutic polypeptides such as liraglutide and KTI are jointly embedded. Through the pH response characteristic and sequential release design of the core-shell structure, KTI is preferentially and rapidly released in the intestinal environment to inhibit local protease activity, then therapeutic polypeptide is slowly released, and active protection and synergistic interaction are achieved. The invention further provides a specific preparation method and parameters. The polypeptide has the advantages of stable structure in a gastric acid environment, targeted release in intestinal tracts, high encapsulation efficiency, capability of avoiding burst release and the like, and provides a new strategy for efficient delivery of oral polypeptide drugs.

The invention provides a composition for treating diabetes as well as a preparation method and application thereof, and belongs to the technical field of medicines. The preparation method comprises the following steps: loading berberine on a milk exosome to prepare a berberine-loaded exosome, loading liraglutide on phycobiliprotein to prepare liraglutide-loaded phycobiliprotein, preparing PEG-COOH, reacting with chitosan to prepare a chitosan-polyethylene glycol graft polymer, embedding the berberine-loaded exosome and the liraglutide-loaded phycobiliprotein, and cross-linking to prepare microspheres. And centrifuging, washing and drying to obtain the composition for treating diabetes. According to the prepared composition for treating diabetes, the loading capacity of the medicine is greatly improved, the carrier also has a very good protection effect on islet cells, so that islet cell injury is repaired, normal insulin secretion of islet cells is promoted, the prepared composition can be orally taken, the medicine effect is greatly improved, the compliance of patients is improved, and the preparation method is suitable for clinical application. The bioavailability is high, and safety and non-toxicity are realized.

The invention discloses lactobacillus delbrueckii with a muscle protection function in a fat reducing period as well as a product and application thereof, belongs to the technical field of microorganisms, and discloses lactobacillus delbrueckii subsp. Lactis Turb8 with the preservation number of CGMCC No.35627. The lactobacillus delbrueckii subsp. Lactis Turb8 has the advantages that the preservation number is CGMCC No.35627; the strain or the preparation thereof can effectively prevent or improve the accompanying problems of muscle loss and function decline in the process of applying fat-reducing drugs such as GLP-1 receptor agonists (such as liraglutide and semeglutide), and the effect of reducing fat but not reducing muscle is achieved. The strain disclosed by the invention can be used for remarkably increasing the lean body mass ratio of a user, increasing the muscle mass of lower limbs, increasing the cross sectional area of muscle fibers and improving muscle function indexes such as strength of four limbs and suspension endurance while keeping the original weight-reducing effect of a fat-reducing medicine. The invention also relates to microbial agents comprising this strain, various preparations, their use in the preparation of products for ameliorating (in particular drug-induced) muscle reduction.

There is provided a pharmaceutical formulation useful for the treatment of a metabolic disorder or condition, the pharmaceutical formulation comprising a plurality of particles suspended in a carrier system, the particles: (a) having an average diameter based on weight, quantity or volume of between about 10 nm and about 700 [mu] m; and (b) comprises a solid core comprising at least one glucagon-like peptide-1 receptor agonist or a pharmaceutically acceptable salt thereof, said solid core being at least partially coated by an inorganic material coating comprising a mixture of (i) zinc oxide; and (ii) one or more other metal oxides and / or metalloid oxides, wherein the atomic ratio ((i): (ii)) is at least about 1: 10 and up to and including about 10: 1. The mixed oxide coated particles are preferably synthesized by vapor phase coating techniques, such as atomic layer deposition. The formulations may provide delayed or sustained release of a glucagon-like peptide-1 receptor agonist to treat metabolic disorders or conditions, such as type 2 diabetes and / or obesity, without burst release effects. The glucagon-like peptide-1 receptor agonist is preferably a liraglutide (liraglutide), and the glucagon-like peptide-1 receptor agonist is preferably a liraglutide (liraglutide).

The present invention provides an injectable depot composition comprising enavogliflozin and a low-dose liraglutide. A combination regimen of enavogliflozin and a low-dose liraglutide provides a synergistic effect in the treatment of obesity compared to the sole administration of either of the drugs. In addition, compared to the sole administration of liraglutide, the administered dose of liraglutide can be reduced, and thus direct causes of gastrointestinal and cardiovascular side effects of liraglutide can be mitigated. In addition, the present invention has the advantage of additionally providing the effect of alleviating metabolic diseases and cardiovascular diseases related to blood glucose, blood lipids, blood pressure, fatty liver, and the like through combined administration with enavogliflozin. Furthermore, the depot composition of enavogliflozin and liraglutide according to the present invention can significantly improve medication convenience and medication adherence for a patient compared to existing liraglutide formulations, which are subcutaneously injected once a day, by unifying the route of administration and improving the administration cycle.

The disclosure provides compositions for Liraglutide drug substance for intranasal application that meets desired physicochemical stability while maintaining solubility of the active pharmaceutical ingredient for a requisite duration. The present disclosure sets forth examples of a Liraglutide drug substance with various excipients (solvents, preservative, stabilizers, penetration enhancers, complexing agents) to achieve desired product attributes for solubility, stability, and pH.

The invention relates to the technical field of biological pharmacy, and particularly discloses targeting drug-loaded nanoparticles for treating rheumatoid arthritis (RA) as well as a preparation method and application thereof, and the technical key points are as follows: on the basis that a GLP-1R agonist (such as liraglutide) is proved to be capable of effectively relieving rheumatoid arthritis symptoms, the targeting drug-loaded nanoparticles can be used for treating rheumatoid arthritis; gLP-1RA is wrapped by the silk fibroin nanoparticles to prepare the drug-loaded nanoparticles, and the drug-loaded nanoparticles can effectively improve the stability of GLP-1RA, prolong retention time in vivo and improve the curative effect of the drug; the drug-loaded nanoparticles and the type II collagen targeting peptide (WYRGRL) are crosslinked, so that the drug-loaded nanoparticles target the articular cartilage, the drug is gathered on the articular cartilage to be attached, the local concentration of the drug and the availability of the drug are further improved, and the curative effect of inhibiting the progress of RA is further enhanced; for lesion facet joints in RA, the treatment scheme of micro-needle administration can realize slow release of drugs, and the micro-needle is convenient to use and is suitable for patients to use at home.

The present invention relates to specific antibodies and use thereof, such as for identifying and / or quantifying liraglutide fibrils and / or semaglutide fibrils.

The present invention relates to specific antibodies and uses thereof, for example, for identifying and / or quantifying liraglutide fibrils and / or semeglutide fibrils.

A pharmaceutical formulation useful for treating metabolic disorders or conditions is provided, comprising a plurality of particles suspended in a carrier system, the particles (a) having an average diameter based on weight, number, or volume of about 10 nm to about 700 μm, and (b) a solid core comprising at least one glucagon-like peptide-1 receptor agonist or a pharmaceutically acceptable salt thereof, at least partially coated with a coating of an inorganic material comprising a mixture of (i) zinc oxide and (ii) one or more other metal and / or metalloid oxides, wherein the atomic ratio ((i):(ii)) is at least about 1:10 and not more than about 10:1. The mixed oxide-coated particles are preferably synthesized by a vapor-phase coating technique, such as atomic layer deposition. The formulation may provide delayed or sustained release of the glucagon-like peptide-1 receptor agonist for treating metabolic disorders or conditions, such as type 2 diabetes and / or obesity, without a burst effect. The glucagon-like peptide-1 receptor agonist is preferably liraglutide.

The present invention provides: a composition for a liraglutide-containing microneedle, which contains liraglutide as an active ingredient, does not cause the denaturation of the active ingredient during manufacturing, and retains stability even after manufacturing; and a liraglutide-containing microneedle which is manufactured using said composition and has enhanced stability. The composition for a microneedle according to the present invention uses a specific combination of a biodegradable polymer, a stabilizer, and an antioxidant, and thus the denaturation of liraglutide, which is an active ingredient, is prevented during the manufacture of the microneedle and the stability of liraglutide is maintained even after the microneedle is manufactured.

The invention belongs to the technical field of biological medicines, and provides application of liraglutide in preparation of a medicine for treating diffuse alveolar hemorrhage and the treatment medicine. The innovative research shows that the liraglutide can be used for treating diffuse alveolar hemorrhage and has an excellent treatment effect, and the brand new treatment thought is convenient in administration, high in safety and low in treatment cost.

The present application relates to a method for removing the main peak residue of liraglutide precursor in a chromatographic column, and the liquid chromatography conditions are as follows: equipment configuration: four-element low-pressure pump or two-element high-pressure pump equipped with flow path switching valve; chromatographic column: InertSil ODS-SP chromatographic column (4.6*250mm, 5um); column temperature: 35-40 DEG C; mobile phase C: sulfate buffer: acetonitrile (82:18), 8M NaOH is adjusted to pH 5.95-6.05; mobile phase D: 50% acetonitrile; flow rate: 1.0ml / min; detection wavelength: 214nm; injection mode: 60% mobile phase D and 40% mobile phase C, isocratic elution for 8min, 0.01M phosphate buffer is injected, 30ul / needle, 1 needle is injected every 8min, a total of 3 needles. The analysis method of the present application can completely remove the main peak residue of liraglutide precursor in the chromatographic column in a short time.

The invention discloses a method for distinguishing biological activities of different GLP-1 analogues. According to the method, liraglutide and semeglutide can be effectively distinguished, tilpotide and HISHS-2001 can be effectively distinguished, accurate matching of treatment requirements, optimization of a medication scheme, promotion of drug research and development and innovation and improvement of clinical medication safety are facilitated, and the application prospect is wide.

A new GLP-1 derivative, which has comparable or better potency, efficacy or efficacy, longer or comparable in vivo duration of action or in vivo half-life, has better or comparable GLP-1 receptor binding affinity, has better or comparable DPP-IV stability, compared to the marketed GLP-1 derivatives such as liraglutide, semaglutide, etc.

The present invention provides an injectable depot composition comprising enavogliflozin and low-dose liraglutide. A combination regimen of enavogliflozin and low-dose liraglutide provides a synergistic effect in the treatment of obesity compared with the single administration of either drug. Furthermore, compared with the single administration of liraglutide, the administered dose of liraglutide can be reduced, and thereby the direct causes of gastrointestinal and cardiovascular side effects of liraglutide can be mitigated. Furthermore, the present invention has the additional advantage of providing an effect for alleviating metabolic diseases and cardiovascular diseases related to blood glucose, blood lipids, blood pressure, fatty liver, and the like through combined administration with enavogliflozin.Furthermore, the depot composition of enavogliflozin and liraglutide according to the present invention can significantly improve treatment convenience and treatment compliance for patients compared to existing liraglutide formulations, which are injected subcutaneously once daily, by unifying the route of administration and increasing the cycle of administration.

Provided are a pharmaceutical composition for preventing and / or treating neurodegenerative diseases and use thereof. The pharmaceutical composition comprises rivastigmine, liraglutide, and derivatives thereof; the pharmaceutical composition further comprises a sustained-release system, the sustained-release system can interact with the rivastigmine, the liraglutide, and the derivatives thereof to form a copolymer that enables sustained drug release, and the sustained-release system is a triblock hydrogel sustained-release system. The combination of the liraglutide and the rivastigmine can ameliorate the learning and memory impairments associated with Alzheimer's disease, with the effect superior to monotherapy and exhibiting a synergistic effect.

The present invention discloses a chromatographic method for simultaneously analyzing liraglutide and its Boc-liraglutide backbone. Specifically, a sample solution containing liraglutide and its Boc-liraglutide backbone is injected into a high-performance liquid chromatograph, and the following high-performance liquid chromatography conditions are used for detection: a bonded silica gel chromatographic column; mobile phase A is an aqueous solution of ammonium dihydrogen phosphate at 0.05 mol / mL - 0.15 mol / mL, and mobile phase B is acetonitrile; among them, the volume ratio of mobile phase B is 15% → 95% for gradient elution. This analysis method has the characteristics of fast analysis speed, accuracy, simplicity, and rapidity, and can play a good role in quality control and analysis and purification during the production process of liraglutide, and has good specificity, high sensitivity, and low cost, etc.

The invention provides a liraglutide bionic functional membrane continuous separation and purification system, the system is used for continuously operating liraglutide separation and purification at 2-8 DEG C, multiple layers of bionic functional membranes are integrated into a micro-channel to form a micro-fluidic chip, an on-line monitoring system is integrated, the separation effect is monitored in real time, and through an intelligent control system, the liraglutide can be continuously separated and purified. Optimizing a separation strategy; each layer of membrane has a specific pore diameter and surface chemical properties, selective separation is carried out aiming at substances with different molecular weights, polarities and biological characteristics, and the multilayer bionic functional membrane is formed by connecting 3-5 layers of multifunctional membranes in series; the technical problems that in an existing liraglutide purification and separation technology, efficiency is low, purity is not high, environmental pollution is serious, rapid high-purity extraction is difficult to achieve, and continuous production is difficult to achieve are solved.

The present invention provides an injectable depot composition comprising linagliptin and low-dose liraglutide. The combination therapy of linagliptin and low-dose liraglutide provides a synergistic effect in the treatment of obesity compared to the administration of each drug alone. In addition, the administration dose of liraglutide can be reduced compared to the administration of liraglutide alone, and thus the direct cause of side effects related to the gastrointestinal system and the cardiovascular system of liraglutide can be reduced. Furthermore, by the combination of linagliptin, it has the advantage of additionally providing an improvement effect on metabolic diseases and cardiovascular diseases related to blood sugar, blood lipids, blood pressure, fatty liver, etc. In addition, compared to the conventional liraglutide dosage form of once-daily subcutaneous injection, the depot composition of linagliptin and liraglutide of the present invention can significantly improve patient convenience and patient compliance by unifying the administration route and improving the administration cycle.

The present invention relates to a method for preparing liraglutide by using a GLP-1 analog. Crude liraglutide is prepared under optimal reaction conditions and with a specific mixing ratio by using a GLP-1 analog, a fatty acid and triethylamine, and is purified through two-step purification, and thus a high-purity liraglutide can be prepared in a high yield.

The present invention relates to an improved process for the preparation of a tetrapeptide of formula (I) wherein R1 and R2 are independently selected from amine protecting groups and R3 is t-Bu or Bn. The invention further relates to a process for preparing liraglutide or a pharmaceutically acceptable salt thereof using the tetrapeptide of formula (I). # imgabs0 #

The present invention relates to a peptide for preventing or treating fibrosis, having the effects of preventing or treating fibrosis by having the property of inhibiting the dissociation of TGF-β1 from LCC by binding to an integrin or the property of inhibiting the change from epithelial cells to mesenchymal cells and promoting the change from mesenchymal cells to epithelial cells, and the property of penetrating cells to bind to Smad2 and Smad3, and thus suppresses the phosphorylation thereof. A peptide according to the present invention exhibits better therapeutic effects than Nintedanib, which was commercialized as a therapeutic agent for pulmonary fibrosis, and Liraglutide, which was commercialized as a therapeutic agent for hepatic fibrosis, and thus can be used as an alternative therapeutic agent to these commercially available therapeutic agents or as an agent for combination therapy with these therapeutic agents.

This application belongs to the field of genetic engineering technology and discloses human enterokinase light chain mutants and their applications. This application involves single-point mutations or multiple rounds of combined mutations based on the wild-type human enterokinase light chain -C112S mutant sequence. The obtained variants have higher specific activity compared to the parent, which is expected to increase unit yield, reduce the residual amount of protease in the final product, and lower product costs. Furthermore, these mutants exhibit high stability in the enzymatic digestion of peptides / proteases, such as liraglutide and smegglutide, GLP-1 analogs, reducing enzyme usage, increasing digestion efficiency, and decreasing the proportion of non-specific products, thereby lowering the production cost of peptide drugs and promoting the rapid development of related industries.

The present invention relates to specific antibodies and their uses, for example for the identification and / or quantification of liraglutide fibrils and / or semaglutide fibrils.

The invention relates to the technical field of biomedicine, in particular to a nano-composite hirudin protein line capable of remodeling glycolipid metabolism and a preparation method of the nano-composite hirudin protein line. The nano-composite hirudin protein line for remodeling glycolipid metabolism is prepared from the following components in parts by weight: 60 to 85 parts of type I collagen line, 5 to 10 parts of recombinant hirudin, 2 to 5 parts of liraglutide, 1 to 5 parts of ursodesoxycholic acid, 1 to 4 parts of polydopamine and 2 to 5 parts of N-hydroxysuccinimide-polyethylene glycol-maleimide. 2-5 parts of phenylboronic acid modified sodium alginate and 2-5 parts of gallic acid chitosan; according to the invention, on-demand accurate release of drugs in a pathological microenvironment is realized, the intervention efficiency is remarkably improved, the side effects of the system are reduced, meanwhile, a collaborative treatment network is formed, root intervention on complex metabolic disorders is realized, the product can actively remodel a local immune microenvironment while delivering the drugs, the process is controllable, the safety is excellent, and the application prospect is wide. And the benefit of traditional wire embedding weight reduction is greatly improved.

The application relates to the technical field of compound synthesis, in particular to a preparation method of a liraglutide side chain and an intermediate thereof. The preparation method of an intermediate 1 forming a liraglutide side chain comprises the following steps: reacting palmitic acid and HOSU to form a reaction crude product, and crystallizing the reaction crude product to form the intermediate 1, wherein the solvent selected for crystallization is a mixed solvent of ester solvents and alkane solvents, the mass ratio of the ester solvents to the alkane solvents is 1:5-1:10, and the structural formula of the intermediate 1 is The intermediate formed by the preparation method has high yield, high purity and low homologous impurity content, so that the liraglutide side chain formed has high purity and low homologous impurity content, thereby a synthesis method suitable for large-scale production of the liraglutide side chain can be obtained.

The present invention provides a method for purifying liraglutide using a selective ion pair reagent in reverse-phase high-performance liquid chromatography to purify raw liraglutide from closely associated impurities.